Damage leads to mutations in the DNA if left uncorrected. These mutations contribute to genomic instability, which can ultimately lead to cancer. Studying the mechanism by which mutations are induced by DNA polymerases can lead to a greater understanding of this process. DNA polymerase Beta (pol-beta) is the main polymerase involved in base excision repair (BER), which is a major mechanism of repairing DNA damage. Pol-beta has no exonuclease activity associated with it; thus, mistakes generated by pol-beta in the DNA repair process may go uncorrected. However, there may exist an exogenous protein that interacts with pol-beta and possesses the required 3'-5' exonuclease activity to remove these misinserted nucleotides. The broad, long-term objective of this research is to study the interactions of other proteins with pol-beta and how they can affect the DNA synthesis fidelity of pol-beta. The specific aims of this proposal are: (1) to characterize the interaction between pol-beta, Mre11, and Rad50 and (2) to test the hypothesis that there exists a functional interaction between Mre11/Rad50 and pol-beta. [unreadable] [unreadable] [unreadable]